Comparison of total and bone-specific alkaline phosphatase in patients with nonskeletal disorder or metabolic bone diseases

To evaluate the diagnostic validity of new assays for bone-specific alkaline phosphatase (BAP), we compared measurements of total alkaline phosphatase (TAP) in serum with results for three different assays of serum BAP in healthy adults (n = 119), patients with chronic nonskeletal disorders (n = 123), and patients with metabolic bone diseases (n = 113). Serum TAP was determined by a standard colorimetric assay, BAP by the methods of lectin precipitation (L-BAP), enzyme immunoassay (E-BAP), and immunoradiometric assay (I-BAP). Impairment of liver function resulted in significant increases of all alkaline phosphatase (AP) measurements, with the smallest changes being exhibited by E-BAP. Compared with the results by TAP, diagnostic sensitivity (i.e., of values exceeding the reference interval) was not improved by BAP, but receiver-operating characteristic (ROC) curve analyses revealed improved discrimination for primary hyperparathyroidism by E-BAP. These results indicate that, in the presence of liver disease, the specificity of AP measurements is improved by measuring BAP. In most other clinical situations, serum TAP appears to provide sufficient clinical information; however, the cross-sectional study design used here allows no statement about the usefulness of BAP in serial measurements.     

Characterization of platelet-activating factor synthesis in glomerular endothelial cell lines

Platelet-activating factor synthesis in two transformed lines of glomerular endothelial cells was characterized and contrasted with platelet-activating factor production in macrovascular-derived endothelial cells as well as with glomerular cells of mesenchymal origin. Platelet-activating factor synthesis was assessed in intact cells and in cell-free preparations. Glomerular endothelial cells constitutively synthesize bio-active alkyl-PAF, and this basal activity can be chronically augmented by various inflammatory and thrombotic agents. In contrast, thrombin-mediated platelet-activating factor formation in bovine pulmonary aortic endothelial cells as well as in glomerular mesangial cells is acute and transient. The potential role of anti-inflammatory prostanoids to function as negative feedback modulators of thrombin- or endothelin-mediated platelet-activating factor synthesis was also investigated, as the synthesis of platelet-activating factor is often associated with the formation of these prostanoids. Indomethacin augmented receptor-mediated platelet-activating factor synthesis while prostanoids of the E and I series reduced agonist-stimulated PAF synthesis. In summary, the unique capacity of glomerular endothelial cells to respond to inflammatory stimuli with sustained platelet-activating factor synthesis is a clear indication of this cell's pivotal role in augmenting the inflammatory response in the limited environment of the glomerulus.     

Endothelium-dependent vasodilatation is impaired in peritoneal dialysis patients

BACKGROUND: Peritoneal dialysis (PD) patients have a high risk of cardiovascular mortality, which is not completely explained by conventional risk factors. Other factors related to chronic renal failure and/or dialysis treatment might lead to endothelial dysfunction, which is associated with an adverse cardiovascular outcome. One such factor is hyperhomocysteinaemia, which has a high prevalence in PD patients. METHODS: A vessel wall movement detector system was used to investigate endothelium-dependent, flow-mediated, and endothelium-independent, glyceryl trinitrate-induced, vasodilatation of the brachial artery in 29 PD patients and 29 control subjects. RESULTS: Endothelium-dependent vasodilatation was markedly reduced in the PD group: 5.7 +/- 1.0% vs 10.4 +/- 1.3% in the control group (P = 0.004). Endothelium-independent vasodilatation was not impaired. Plasma total homocysteine was elevated in the PD patients (45.2 +/- 6.2 micromol/l), but was not related to endothelium-dependent vasodilatation. CONCLUSION: Chronic peritoneal dialysis patients have impaired endothelium-dependent vasodilatation, which may reflect an increased susceptibility for the development of atherosclerosis and thrombosis.     

Hippocampal atrophy in normal aging. An association with recent memory impairment

OBJECTIVE: To estimate the prevalence of radiographically detectable hippocampal atrophy (HA) in a normal aging sample and to test whether such atrophy is associated with memory dysfunction. DESIGN: One hundred fifty-four medically healthy and cognitively normal elderly persons (aged 55 to 88 years) received magnetic resonance imaging and/or computed tomographic scans designed to identify HA. One hundred forty-five of these subjects also underwent psychometric tests of memory function. Multivariate analyses of variance were used to evaluate differences in memory performance between subjects with and without HA. SETTING: This study was conducted at a research clinic for the investigation of age-associated neuropsychological and neuroradiologic changes. PARTICIPANTS: Based on the following criteria, 154 subjects were consecutively selected from a larger group of elderly research volunteers participating in a study of normal aging: age of 55 years or greater; Global Deterioration Scale score of 2 or less; and Mini-Mental State examination score of 28 or greater. Subjects with evidence for significant medical, psychiatric, or neurologic disease were excluded. MAIN OUTCOME MEASURES: Outcome measurements included individual psychometric test scores and computed tomographic-magnetic resonance imaging hippocampal atrophy ratings. RESULTS: Nearly 33% of the subjects had radiographic evidence for HA. The prevalence of HA increased significantly with age and was more common in male than female subjects. After controlling for age, level of education, and vocabulary, subjects with HA were found to perform more poorly on tests of recent (secondary) verbal memory when compared with subjects without HA (P < .01). No significant differences were found for tests of immediate (primary) memory. CONCLUSION: We conclude that HA is a common accompaniment of normal aging and is associated with mild memory impairment. Additional research is needed to determine whether HA constitutes a significant risk for future dementia.     

Activation of auditory cortex during silent lipreading

Watching a speaker's lips during face-to-face conversation (lipreading) markedly improves speech perception, particularly in noisy conditions. With functional magnetic resonance imaging it was found that these linguistic visual cues are sufficient to activate auditory cortex in normal hearing individuals in the absence of auditory speech sounds. Two further experiments suggest that these auditory cortical areas are not engaged when an individual is viewing nonlinguistic facial movements but appear to be activated by silent meaningless speechlike movements (pseudospeech). This supports psycholinguistic evidence that seen speech influences the perception of heard speech at a prelexical stage.     

Exit of the pre-TCR from the ER/cis-Golgi is necessary for signaling differentiation, proliferation, and allelic exclusion in immature thymocytes

A major issue is whether surface expression of the pre-TCR is necessary for signaling the development of immature thymocytes. To address this question, we generated transgenic mice expressing a TCRbeta chain that had a strong endoplasmic reticulum (ER) retrieval signal (TCRbetaER) and that was expressed intracellularly but failed to reach the cell surface. In TCRbetaER transgenic mice, there was a failure of allelic exclusion. Also, the transgene failed to rescue the developmental defects observed in TCRbeta-null mice. In contrast, TCRbeta transgenes with a mutant ER retrieval sequence or lacking this sequence signaled efficient allelic exclusion and suppressed the TCRbeta-/- defect. These data show that exit of the pre-TCR from the ER/cis-Golgi is required for progression through the double-negative thymocyte checkpoint.     

Differential responses in anterior pituitary luteinizing hormone (LH) content and LH beta- and alpha-subunit mRNA, and plasma concentrations of LH and testosterone, in bulls treated with the LH-releasing hormone agonist deslorelin

Tooth loss diminishes oral function and quality of life, and national health targets aim to reduce population levels of tooth loss. OBJECTIVES: The purpose of this study was to determine tooth loss incidence and predictors of tooth loss among older adults in South Australia. METHODS: Data were obtained from a cohort study of a stratified random sample of community-dwelling dentate people aged 60+ years. Interviews and oral examinations were conducted among 911 individuals at baseline and among 693 of them (76.1%) 2 years later. Incidence rates and relative risks were calculated for population subgroups and multivariate logistic regression was used to construct risk prediction models. A method was developed to calculate 95% confidence intervals (95% CI) for relative risks (RR) from logistic regression models using a Taylor series approximation. RESULTS: Some 19.5% (95% CI = 15.4-23.6%) of people lost one or more teeth during the 2 years. Men, people with a recent extraction, people who brushed their teeth infrequently, smokers and people born outside Australia had significantly (P < 0.05) greater risk of tooth loss. Baseline clinical predictors of tooth loss included more missing teeth, retained roots, decayed root surfaces, periodontal pockets and periodontal recession. In a multivariate model that controlled for baseline clinical predictors, former smokers (RR = 2.55, 95% CI = 1.48-4.40) and current smokers (RR = 2.06, 95% CI = 0.92-4.62) had similarly elevated risks of tooth loss compared with non-smokers. CONCLUSIONS: The findings from this population suggest that a history of smoking contributes to tooth loss through mechanisms in addition to clinical disease processes alone.     

Immunohistochemical expression of p53 and c-erbB-2 in breast carcinoma: relation with epidemiologic factors, histologic features and prognosis

We have performed immunohistochemical staining for p53 and c-erbB-2 on formaldehyde-fixed, paraffin-embedded primary invasive ductal carcinomas from 112 patients, with a minimal follow-up time of 60 months. All of them had received postoperative chemoradiation therapy. We have analyzed the association of these factors with epidemiologic risk factors, histopathologic features and hormonal receptor status and the influence on prognosis. Our results indicate that the expression of c-erbB-2 protein defines a group of node-negative patients with poor prognosis. The overexpression of c-erbB-2 has shown a significant association with estrogen receptor status (those tumors expressing c-erbB-2 are usually estrogen receptor negative), presence of fibrosis and lymphoplasmacytoid infiltrates. P53 expression has shown no relation either with prognosis or with any other histopathologic or clinical feature. The only factors with prognostic influence in our series have been tumor size, the presence of node metastases, TNM stage and the prognostic morphometric index (Baak's index), apart from c-erbB-2 in node-negative patients. However, only the TNM stage showed an independent association with prognosis after a multivariate analysis. In summary, in our experience the expression of p53 protein has no prognostic influence on breast carcinoma, and TNM stage remains to be as the most powerful prognostic factor in these patients.     

Second primitive malignant tumour in patients with gynaecological cancer

OBJECTIVE: The purpose of this study was to characterise the occurrence of multiple primitive gynaecological malignant neoplasias, restricted to the genital tract and breast or associated with other organs, and to detect which types of association are most frequent concerning location, histology and staging. POPULATION AND METHODS: The records of patients with gynaecological cancer at the Portuguese Institute of Oncology--Lisbon Centre, between 1986 and 1993 were used in this study. RESULTS: Of the 10,746 women with gynaecological cancer, 91 (0.8%) were found to have a second primitive malignant neoplasia. Of these neoplasias, 64% (58 cases) were also located at a gynaecological site. The most frequent associations were endometrium/breast (13 cases), bilateral breast (12 cases) and ovary/endometrium (11 cases). The majority of primitive multiple gynaecological tumours were synchronous. Regarding gynaecological cancer and non-gynaecological cancer, in 28 cases (31%), the most common non-gynaecological location was the colon/rectum. Five patients had triple tumours. CONCLUSION: Although these situations are relatively rare the possibility of multiple primitive cancers should be considered with the presence of malignant tumours in two or more organs. This distinction between multiple primitive or metastatic cancers could be important for treatment as well as prognosis.